PROJECT SUMMARY/ABSTRACT The goal of this Mentored Clinical Scientist Research Development Award (K08) is to train the candidate in theory, methodology, and statistics. This training will prepare the candidate for a career as an independent investigator. The candidate will develop expertise needed to launch a program of research examining shared mechanisms underlying gender specific pathways to substance use and psychopathology co-occurrence. To facilitate this overarching goal, the proposed K08 project will focus on identifying shared etiological vulnerabilities for tobacco use and depression among emerging adult females. Research on this topic is timely given that, while historically males have had higher reported rates of tobacco use than females, the gender gap in tobacco use is closing (especially among emerging adults ages18-26). Thus, understanding the underlying mechanisms that influence young women to use tobacco is an important public health concern. Two issues complicate female tobacco use: 1) there is a high degree of polysubstance use (most notably, alcohol and/or cannabis); and 2) female smokers are over twice as likely to exhibit depression (relative to male smokers). Studies that fail to account for polysubstance use and co-occurring depression may have limited public health impact, as results may not be generalizable. The research proposed in this K08 application seeks to elucidate the underpinnings of co-occurring substance use and depression by: 1) identifying proximal shared or transdiagnostic risk factors; and 2) exploring how these risk factors unfold in the natural environment. Specifically, individual differences in response to stress and cognitive control are hypothesized to predict both substance use and depressive symptoms; and these effects are expected to be mediated through rumination (repetitive negative thinking; an understudied process in the substance use field) among females, but not males. Original data collection is proposed to sample a hundred and six 18-26 year-old substance using emerging adults who will participate in: a laboratory baseline assessment followed by intensive ecological sampling methods. At baseline: 1) stress response will be assessed via a laboratory stress paradigm with collection of salivary cortisol; and 2) a computerized assessment of cognitive control will be conducted. After baseline, a 30-day smartphone application-based ecological momentary assessment (EMA) protocol will be used to assess ?real-time? rumination, substance use (tobacco, alcohol, cannabis), and depressive symptoms. This K08 will provide the candidate with mentored research experience to acquire new skills in: 1) Theory (broad substance use models); 2) Methodology (administration of a laboratory stressor; EMA data collection); and 3) Statistics (EMA analyses); as well as 4) Professional Development (manuscripts & grant writing). Results will be used as pilot data for a R01 application that will aim to identify gender specific etiological pathways in the emergence of co-occurring substance use and broad psychopathological conditions. This line of research has the potential to inform etiologically driven gender-sensitive prevention and intervention efforts.